Increased physical activity is associated with a decreased risk of several types of cancer, but the underlying mechanisms for these associations are still poorly understood. The National Cancer Institute has identified investigations into the mechanisms linking energy balance and its components (physical activity, diet, obesity) and cancer as being a high priority for research. Physical activity may alter cancer risk through diverse mechanisms such as effects on insulin resistance, steroid hormones, and various growth factors. Less explored potential mechanisms include angiogenesis, which is required for tumor growth promotion. Physical activity may affect these biomarkers through changes in adiposity. Therefore, we propose to investigate the effect of moderate intensity exercise on blood levels of cancer biomarkers related to angiogenesis in 170 overweight/obese sedentary women who were part of a randomized controlled exercise intervention trial (86 Exercise Intervention and 84 Controls; Physical Activity for Total Health, R01 CA 69334; PI: McTiernan, Seattle, USA). The exercise intervention was a 1-year moderate intensity facility and home-based aerobic exercise program, 45 minutes/day, 5 days/week vs. stretching control. 98% of participants completed 12-month trial data collection and the intervention participants completed a mean 88% of the goal 225 minutes/week of activity. These women are well characterized in terms of self-reported diet and physical activity, anthropometry, body composition, and blood biomarkers, including sex hormones, insulin, C-reactive protein, and others. The specific aims of the study are to test the effect of 1-year exercise intervention vs. control in postmenopausal sedentary, overweight/obese women on serum concentrations of the angiogenic markers vascular endothelial growth factor (VEGF), osteopontin, pigment epithelium-derived factor (PEDF) and plasminogen activator inhibitor-1(PAI-1). To help understand the biologic mechanism, we will explore whether intervention effects differ by BMI or body composition prior to the intervention, or are dependent on amount of physical activity performed or on changes in body composition during the trial. The proposed study represents a unique opportunity to expand knowledge about the effects of physical activity on angiogenesis-related biomarkers, in a cost-effective and comprehensive manner by using an existing resource.